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Bitter gourd is an economically important horticultural crop for its edible and medicinal value. However, the regulatory mechanisms of bitter gourd in response to cold stress are still poorly elucidated. In this study, phytohormone determination and comparative transcriptome analyses in XY (cold-tolerant) and QF (cold-sensitive) after low temperature treatment were conducted. Under cold stress, the endogenous contents of abscisic acid (ABA), jasmonic acid (JA) and salicylic acid (SA) in XY were significantly increased at 24 h after treatment (HAT), indicating that ABA, JA and SA might function in regulating cold resistance. RNA-seq results revealed that more differentially expressed genes were identified at 6 HAT in QF and 24 HAT in XY, respectively. KEGG analysis suggested that the plant hormone signal transduction pathway was significantly enriched in both genotypes at all the time points. In addition, transcription factors showing different expression patterns between XY and QF were identified, including CBF3, ERF2, NAC90, WRKY51 and WRKY70. Weighted gene co-expression network analysis suggested MARK1, ERF17, UGT74E2, GH3.1 and PPR as hub genes. These results will deepen the understanding of molecular mechanism of bitter gourd in response to cold stress and the identified genes may help to facilitate the genetic improvement of cold-resistant cultivars., (© 2024. The Author(s).)

Background: Ribosome-inactivating proteins (RIPs) have been reported to exert antitumor and anti-virus activities. A recent patent CN202011568116.7 has developed a new method to prepare Momordica anti-HIV protein of 30 kDa (MAP30). MAP30 is a type I RIP, which kills various tumor cells through the N-glycosidase activity and irreversibly inhibits protein synthesis., Objective: To assess the potential role of MAP30 in inducing apoptosis of human hepatocellular carcinoma HCC-LM3 cells and elucidate the molecular mechanism of MAP30., Methods: CCK-8 assay was used to assess the proliferation of HCC-LM3 cells. Flow cytometry was used to measure the cycle, the level of ROS and apoptosis in HCC-LM3 cells. Western blots was used to measure protein levels., Results: Treatment with MAP30 reduced survival and proliferation of human liver cancer HCCLM3 cells in a dose-dependent manner. PI staining showed cell cycle arrest in G0/G1 phase. Furthermore, MAP30 increased the level of ROS in HCC-LM3 cells in 24 h treatment. To further confirm the role of MAP30 in inducing cell apoptosis, immunoblotting was carried out to detect the change of apoptosis-related proteins including PARP poly (ADP-ribose) polymerase (PARP- 1), Casepase3 and Cleaved-Caspase9. We found that PARP-1 and Caspase-3 were downregulated, whereas Cleaved-Caspase9 was up-regulated in HCC-LM3 cells treated with MAP30., Conclusion: This study indicated that MAP30 has the potential to be a novel therapeutic agent for human hepatocellular carcinoma., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Bitter gourd (Momordica charantia L.), belonging to family Cucurbitaceae, is a good source of carbohydrates, proteins, vitamins, minerals, and bioactive compounds. In the present study, fruits (and its parts-epicarp, mesocarp, endocarp, seed, and whole fruit) of 56 accessions and 4 cultivars of Momordica spp. were assayed and compared for macro-minerals magnesium (Mg), potassium (K), sodium (Na), phosphorus (P), and calcium (Ca), and microminerals iron (Fe), zinc (Zn), manganese (Mn), and copper (Cu). Potassium was the most abundant macro-mineral found in whole fruit ranging from 78.40 to 483.49 mg/100 g dry weight (DW), followed by Mg (13.23-101.70 mg/100 g DW) in epicarp, P (32.22-98.24 mg/100 g DW) in endocarp, Ca (23.41-71.39 mg/100 g DW) in whole fruit, and Na (6.09-18.56 mg/100 g DW) in epicarp. The concentration of microminerals was recorded higher in seeds compared to other fruit parts. Levels of Fe were higher (0.76-6.14 mg/100 g DW), followed by Zn (0.87-2.64 mg/100 g DW), Cu (137.68-525.45 µg/100 g DW), and Mn (46.92-179.05 µg/100 g DW). The analysis depicted bitter gourd to be a potential source of both macro-minerals (K and Mg) and microminerals (Fe and Zn). The consumption of bitter gourd could be a health-promoting strategy to meet daily dietary intake requirements of essential minerals for human health., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

An 8-week feeding trial was conducted to explore the feasibility of Momordica charantia saponins (MCS) administration to facilitate the protein-sparing action of high carbohydrate in diets for juvenile common carp (Cyprinus carpio) with initial mass of 5.41 ± 0.02 g. Based on our previous study, four diets with different the ratio of protein and carbohydrate (P/C ratio) were designed: 32%P/40%C, 30%P/43%C, 28%P/46%C, 28%P/46%C supplemented with 0.16% MCS (28%P/46%C + MCS). Each diet treatment was divided into 3 replicates. Results revealed that 30%P/43%C group increased growth performance and intestinal digestion, decreased intestinal inflammation, and optimized the intestinal microbiota compared to 32%P/40%C group, which presented the stronger protein-sparing action of high carbohydrate. But if the P/C ratio reduced to 28%P/46%C or less, the saving action would be restrained. However, compared to the 30%P/43%C and 28%P/46%C groups, 28%P/46%C + MCS group significantly elevated growth performance and activities of digestive enzymes and antioxidative enzymes, whilst the opposite trend occurred in the contents of glucose, triglyceride, total cholesterol, low density lipoprotein cholesterol, blood urea nitrogen, glutamic oxalacetic transaminase, glutamic-pyruvic transaminase and malondialdehyde. In addition, 28%P/46%C + MCS group markedly upregulated the expressions of GH/IGF axis genes, genes involved in protein synthesis, antioxidant genes and anti-inflammatory cytokine, whilst the opposite trend occurred in the expressions of pro-inflammatory cytokines. Moreover, 28%P/46%C + MCS group obtained the remarkably higher Enterococcus proportion and lower Lactococcus proportion compared to the 30%P/43%C and 28%P/46%C groups, whereas the opposite occurred in 30%P/43%C group, which indicated that there existed differences in the improvement mechanism on intestinal microflora composition between MCS and appropriate P/C ratio. Combined with the above mentioned changes in our research, we concluded that 0.16% MCS administration in a 28%P/46%C diet could facilitate the protein-sparing action of high carbohydrate in diets for common carp, which could decrease the 5% dosage of soybean meal and synchronously reduce the 4% crude protein of diets without affecting the growth and immune ability for common carp., Competing Interests: Declaration of competing interest All of the authors declare no conflicts of interest., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

The use of coumarin (COU) to alleviate the phytotoxic effects of salinity has great potential in improving the phytoremediation of saline and alkaline soils. 30-day bitter gourd plants were exposed to 15 dS m ‒1 salinity of neutral (NaCl and Na 2 SO 4 ) and alkaline (Na 2 CO 3 and NaHCO 3 ) salts. 60-day plants were harvested to record different growth, physiological and biochemical attributes. Salinity significantly subsided plant growth, chlorophyll, photosynthesis, and nutrient acquisition. Salinity induced notable oxidative damage in plants that displayed higher relative membrane permeability (RMP), accumulated elevated ROS (H 2 O 2 and O 2 •‒ ) and MDA levels alongside intensified lipoxygenase (LOX) activity. The production of cytotoxic methylglyoxal was also significantly higher in plants under salinity. COU seed priming (50, 100 and 150 mg L ‒1 ) promoted plant growth by circumventing oxidative injury and intensifying oxidative defense. Further, COU maintained the intricate balance between reduced (GSH) and oxidized (GSSG) glutathione to diminish ion excess toxicity, thereby facilitating the phytoremediation of saline soils. The lower doses of COU promoted methylglyoxal and ROS detoxification systems that, in turn, lessened the phytotoxic effects of salinity. COU restored ions homeostasis by augmenting osmotic adjustment in plants under salinity., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Sugar-stabilised nanomaterials have received a lot of attention in cancer therapy in recent years due to their pronounced application as specific targeting agents and maximizing their therapeutic potential while bypassing off-target effects. Lectins, the carbohydrate-binding proteins, are capable of binding to receptors present on the target cell/tissue and interact with transformed glycans better than normal cells. Besides some of the lectins exhibit anticancer activity. Conjugating sugar-stabilised NPs with lectins there for is expected to multiply the potential for the early diagnosis of cancer cells and the specific release of drugs into the tumor site. Because of the prospective applications of lectin-sugar-stabilised nanoparticle conjugates, it is important to understand their molecular interaction and physicochemical properties. Momordica charantia Seed Lectin (MCL) is a type II RIP and has been known as an anti-tumor agent. Investigation of the interaction between sugar-stabilised silver nanoparticles and MCL has been performed by fluorescence spectroscopy to explore the possibility of creating an effective biocompatible drug delivery system against cancer cells. In this regard interaction between lectin and NPs should be well-preserved, while recognizing the specific cell surface sugar. Therefore experiments were carried out in the presence and absence of specific sugar galactose. Protein intrinsic fluorescence emission is quenched at ~ 20% at saturation during the interaction without any significant shift in fluorescence emission maximum. Binding experiments reveal a good affinity. Tetrameric MCL binds to a single nanoparticle. Stern-Volmer analysis of the quenching data suggests that the interaction is via static quenching leading to complex formation. Hemagglutination experiments together with interaction studies in the presence of specific sugar show that the sugar-binding site of the lectin is distinct from the nanoparticle-binding site and cell recognition is very much intact even after binding to AgNPs. Our results propose the possibility of developing MCL-silver nanoparticle conjugate with high stability and multiple properties in the diagnosis and treatment of cancer., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Objective: We investigate the effect of Momordica charantia (MC) against ovarian ischemia-reperfusion injury (IRI)., Materials and Methods: Forty-eight Sprague Dawley female rats were divided into 6 groups. 3 hours ischemia/3 hours reperfusion was conducted. Before and/or after IR, 600 mg/kg MC were introduced to rats via an orogastric tube. At the end of the experiment, total serum antioxidant/oxidant status (TAS/TOS) and Anti-Mullerian Hormone (AMH) level were measured. Ovarian histopathology and APAF-1 expression level were analyzed., Results: TAS and AMH levels were the lowest, while TOS level and OSI were the highest in the IR group. TAS and AMH levels were higher, and TOS levels and OSI were lower in MC-treated groups compared to IR group. Follicular degeneration, granulosa and stromal cell degeneration, mononuclear cell infiltration and vascular congestion and dilatation were observed in the IR group. Ovarian histopathology was improved in groups that received MC extract. APAF-1 immune activity was intense in IR and MC+IR groups while decreased in the groups treated with MC extract after IRI. MC treatment downregulated APAF-1 protein after IRI., Conclusions: MC extract restored negative biochemical and histochemical changes caused by IRI due to its antioxidant properties and supported cell survival by suppressing APAF-1 expression.

Aging is widely thought to be associated with oxidative stress. Momordica charantia (MC) is a classic vegetable and traditional herbal medicine widely consumed in Asia, and M. charantia polysaccharide (MCP) is the main bioactive ingredient of MC. We previously reported an antioxidative and neuroprotective effect of MCP in models of cerebral ischemia/reperfusion and hemorrhage injury. However, the role played by MCP in neurodegenerative diseases, especially during aging, remains unknown. In this study, we investigated the protective effect of MCP against oxidative stress and brain damage in a D-galactose-induced aging model (DGAM). The Morris water maze test was performed to evaluate the spatial memory function of model rats. The levels of malondialdehyde (MDA), glutathione (GSH), and superoxide dismutase (SOD) were measured and telomerase activity was determined. The results showed that MCP treatment attenuated spatial memory dysfunction induced by D-galactose. In addition, MCP increased antioxidant capacity by decreasing MDA and increasing SOD and GSH levels. MCP treatment also improved telomerase activity in aging rats. Mechanistically, MCP promoted the entry of both Nrf2 and β-Catenin into the nucleus, which is the hallmark of antioxidation signaling pathway activation. This study highlights a role played by MCP in ameliorating aging-induced oxidative stress injury and reversing the decline in learning and memory capacity. Our work provides evidence that MCP administration might be a potential antiaging strategy., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

The platelets play a crucial role in the progression of multiple medical conditions, such as stroke and tumor metastasis, where antiplatelet therapy may be a boon for treating these diseases. In this study, we have attempted to study the effects of extracted Momordica charantia exosomes (MCEs) on platelet activation, adhesion, and aggregation. Adult platelets isolated from healthy individuals were dose-dependently treated with MCEs (0.1, 40, and 200 μg/ml). We performed flow cytometry to detect the expression of platelet activation protein marker-activated GP IIb/IIIa (PAC-1) and P-selectin (CD62P). Platelet adhesion was analyzed through fluorescence labeling assays. The effect of MCEs on platelet-mediated cell migration of HCT116 cells was observed by transwell. Furthermore, the MCAO model of Sprague-Dawley rats was used to observe the effect of MCEs (200, 400, and 800 μg/kg) on platelet aggregation and maximum thrombotic agglutination in vivo . The results showed that 200 μg/ml MCEs exerted the most pronounced effect on platelet activation, adhesion, and aggregation. Experiments on animals showed that MCEs significantly inhibited platelet aggregation and attenuated the maximum thrombus agglutination. We concluded that MCEs inhibited platelet activation, adhesion, aggregation, and platelet-mediated migration of HCT116 cells, indicating the potential role MCEs may play in the treatment of stroke and tumor metastasis., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)

The bitter gourd seed oil, rich in conjugated fatty acids, has therapeutic value to treat cancer, obesity, and aging. It also has an industrial application as a drying agent. Despite its significance, genomics studies are limited, and the genes for seed oil biosynthesis are not fully understood. In this study, we assembled the fruit transcriptome of bitter gourd using 254.5 million reads (Phred score > 30) from the green rind, white rind, pulp, immature seeds, and mature seeds. It consisted of 125,566 transcripts with N50 value 2,751 bp, mean length 960 bp, and 84% completeness. Transcript assembly was validated by RT-PCR and qRT-PCR analysis of a few selected transcripts. The transcripts were annotated against the NCBI non-redundant database using the BLASTX tool (E-value < 1E-05). In gene ontology terms, 99,443, 86,681, and 82,954 transcripts were classified under biological process, molecular function, and cellular component. From the fruit transcriptome, we identified 26, 3, and 10 full-length genes coding for all the enzymes required for synthesizing fatty acids, conjugated fatty acids, and triacylglycerol. The transcriptome, transcripts with tissue-specific expression patterns, and the full-length identified from this study will serve as an important genomics resource for this important medicinal plant., (© 2022. The Author(s).)

Background: Melatonin is a multi-functional molecule widely employed in order to mitigate abiotic stress factors, in general and salt stress in particular. Even though previous reports revealed that melatonin could exhibit roles in promoting seed germination and protecting plants during various developmental stages of several plant species under salt stress, no reports are available with respect to the regulatory acts of melatonin on the physiological and biochemical status as well as the expression levels of defense- and secondary metabolism-related related transcripts in bitter melon subjected to the salt stress., Results: Herewith the present study, we performed a comprehensive analysis of the physiological and ion balance, antioxidant system, as well as transcript analysis of defense-related genes (WRKY1, SOS1, PM H + -ATPase, SKOR, Mc5PTase7, and SOAR1) and secondary metabolism-related gene expression (MAP30, α-MMC, polypeptide-P, and PAL) in salt-stressed bitter melon (Momordica charantia L.) plants in response to melatonin treatment. In this regard, different levels of melatonin (0, 75 and 150 µM) were applied to mitigate salinity stress (0, 50 and 100 mM NaCl) in bitter melon. Accordingly, present findings revealed that 100 mM salinity stress decreased growth and photosynthesis parameters (SPAD, Fv / Fo , Y(II)), RWC, and some nutrient elements (K + , Ca 2+ , and P), while it increased Y(NO), Y(NPQ), proline, Na + , Cl - , H 2 O 2 , MDA, antioxidant enzyme activity, and lead to the induction of the examined genes. However, prsiming with 150 µM melatonin increased SPAD, Fv / Fo , Y(II)), RWC, and K + , Ca 2+ , and P concentration while decreased Y(NO), Y(NPQ), Na + , Cl - , H 2 O 2 , and MDA under salt stress. In addition, the antioxidant system and gene expression levels were increased by melatonin (150 µM)., Conclusions: Overall, it can be postulated that the application of melatonin (150 µM) has effective roles in alleviating the adverse impacts of salinity through critical modifications in plant metabolism., (© 2022. The Author(s).)

Anti-aging is a challenging and necessary research topic. Momordica charantia L. is a common edible medicinal plant that has various pharmacological activities and is often employed in daily health care. However, its anti-aging effect on mice and the underlying mechanism thereof remain unclear. Our current study mainly focused on the effect of Momordica charantia L. on d-galactose-induced subacute aging in mice and explored the underlying mechanism. UHPLC-Q-Exactive Orbitrap MS was applied to qualitatively analyze the chemical components of Momordica charantia L. ethanol extract (MCE). A subacute aging mice model induced by d-galactose (d-gal) was established to investigate the anti-aging effect and potential mechanism of MCE. The learning and memory ability of aging mice was evaluated using behavioral tests. The biochemical parameters, including antioxidant enzyme activity and the accumulation of lipid peroxides in serum, were measured to explore the effect of MCE on the redox imbalance caused by aging. Pathological changes in the hippocampus were observed using hematoxylin and eosin (H&E) staining, and the levels of aging-related proteins in the PI3K/AKT signaling pathway were assessed using Western blotting. The experimental results demonstrated that a total of 14 triterpenoids were simultaneously identified in MCE. The behavioral assessments results showed that MCE can improve the learning and memory ability of subacute mice. The biochemical parameters determination results showed that MCE can improve the activity of antioxidant enzymes and decrease the accumulation of lipid peroxides in aging mice significantly. Furthermore, aging and injury in the hippocampus were ameliorated. Mechanistically, the results showed a significant upregulation in the protein expression of P-PI3K/PI3K and P-AKT/AKT (p < 0.01), as well as a significant reduction in cleaved caspase-3/caspase-3, Bax and P-mTOR/mTOR (p < 0.01). Our results confirm that MCE could restore the antioxidant status and improve cognitive impairment in aging mice, inhibit d-gal-induced apoptosis by regulating the PI3K/AKT signaling pathway, and rescue the impaired autophagy caused by mTOR overexpression, thereby exerting an anti-aging effect.

Bitter melon (Momordica charantia L.) has been shown to have various health-promoting activities, including antidiabetic and hypoglycaemic effects. Improvement in insulin sensitivity and increase in glucose utilisation in peripheral tissues have been reported, but the effect on insulin secretion from pancreatic β-cells remains unclear. In this study, we investigated the effect of bitter melon fruit on insulin secretion from β-cells and the underlying mechanism. The green fruit of bitter melon was freeze-dried and extracted with methanol. The bitter melon fruit extract (BMFE) was fractionated using ethyl acetate (fraction A), n-butanol (fraction B) and water (fraction C). Insulin secretory capacity from INS-1 rat insulinoma cell line and rat pancreatic islets, as well as glucose tolerance in rats by oral glucose tolerance test (OGTT), was measured using BMFE and fractions. ATP production in β-cells was also examined. BMFE augmented insulin secretion from INS-1 cells in a dose-dependent manner. The significant augmentation of insulin secretion was independent of the glucose dose. Fraction A (i.e. hydrophobic fraction), but not fractions B and C, augmented insulin secretion significantly at the same level as that by BMFE. This finding was also observed in pancreatic islets. In OGTT, BMFE and fraction A decreased blood glucose levels and increased serum insulin levels after glucose loading. The decrease in blood glucose levels was also observed in streptozotocin-induced diabetic rats. In addition, BMFE and fraction A increased the ATP content in β-cells. We concluded that hydrophobic components of BMFE increase ATP production and augment insulin secretion from β-cells, consequently decreasing blood glucose levels.

Diabetic nephropathy is an inflammatory immune disorder accompanying diabetes. A trypsin inhibitor of Momordica charantia , mcIRBP, is an abundant 68 amino acid residue protein that interacts with the insulin receptor. Here the long-term effects of mcIRBP on the improvement of diabetic nephropathy were determined. Type 2 diabetic mice ( db / db ) were given mcIRBP administered orally for 12 consecutive weeks. Histological changes relating to the kidney were evaluated using Periodic Acid Schiff and Sirius Red staining. The mcIRBP-affected gene expression profile in the kidney was determined using RNA-Seq. The renoprotective mechanism of mcIRBP was elucidated based on ex vivo imaging and immunohistochemistry staining. Data showed that the administration of mcIRBP significantly decreased fasting blood glucose and glycated hemoglobin A1c (HbA1c) levels by 61% and 27.92%, respectively, suggesting that mcIRBP exhibited HbA1c-lowering abilities in diabetic mice. RNA sequencing (RNA-Seq) analysis showed that the majority of the mcIRBP-affected biological pathways were associated with inflammation and immunity, and the nuclear factor-κB (NF-κB) signaling pathway was significantly affected by mcIRBP. Ex vivo imaging showed that mcIRBP significantly decreased NF-κB-driven bioluminescence in the kidney by 46 ± 23%. The levels of the renal function indices, Evans blue dye content, fibrosis lesions, and cytokine expression were significantly decreased by mcIRBP, suggesting that mcIRBP improved vascular leakage and the pathological and inflammatory characteristics of diabetic nephropathy. This is the first study reporting that, in addition to blood glucose regulation, mcIRBP can act as a novel renoprotective and anti-inflammatory polypeptide, thereby improving diabetic nephropathy in db / db mice. In addition, this study suggested that there was a potential medicinal use of mcIRBP for the management of diabetes and its complications.

Among the risk factors affecting the development of cancer, nutritional factors occupy a significant place. Pomegranate seed oil (PSO) and bitter melon extract (BME), used for ages in folk medicine, are nowadays used in the prevention of many diseases and as ingredients of dietary supplements. Despite numerous publications on these raw materials or their active substances, their mechanism of action in various pathological states has not been recognized yet, nor has the safety of their simultaneous use been evaluated. The study aimed to assess how dietary supplementation with either PSO, with BME, or both, affects fatty acids' profiles and their metabolism in hepatic microsomes, as well as the activity of selected microsomal enzymes (COX-2 and CYP1B1). Experimental animals (Sprague-Dawley rats) were divided into eight parallel experimental groups, differing in applied dietary modifications (control, PSO, BME and both PSO and BME) and introduction of chemical carcinogen-7,12-dimethylbenz[a]nthracene. Obtained results indicated the pronounced effect of the cancerous process on lipid metabolism and demonstrated the antagonistic effect of applied dietary supplements on the content of individual fatty acids and the activity of CYP1B1 and COX-2. The applied broad analytical approach and chemometric data analysis confirmed that raw materials, for which potential cancer prevention has been previously demonstrated, may differ in effects depending on the coexisting pathological state.

Background: Plant-derived extracellular vesicles (PDEVs) have been exploited for cancer treatment with several benefits. Bitter melon is cultivated as a vegetable and folk medicine with anticancer and anti-inflammatory activities. 5-Fluorouracil (5-FU) is widely used for cancer treatment. However, 5-FU-mediated NOD-like receptor family pyrin domain containing 3 (NLRP3) inflammation activation induced the resistance of oral squamous cell carcinoma (OSCC) cells to 5-FU. In this study, we explored the potential of bitter melon-derived extracellular vesicles (BMEVs) for enhancing the therapeutic efficacy and reduce the resistance of OSCC to 5-FU., Results: Herein, we demonstrate that bitter melon derived extracellular vesicles (BMEVs), in addition to their antitumor activity against OSCC have intrinsic anti-inflammatory functions. BMEVs induced S phase cell cycle arrest and apoptosis. Apoptosis induction was dependent on reactive oxygen species (ROS) production and JUN protein upregulation, since pretreatment with N-acetyl cysteine or catechin hydrate could prevent apoptosis and JUN accumulation, respectively. Surprisingly, BMEVs significantly downregulated NLRP3 expression, although ROS plays a central role in NLRP3 activation. We further assessed the underlying molecular mechanism and proposed that the RNAs of BMEVs, at least in part, mediate anti-inflammatory bioactivity. In our previous studies, NLRP3 activation contributed to the resistance of OSCC cells to 5-FU. Our data clearly indicate that BMEVs could exert a remarkable synergistic therapeutic effect of 5-FU against OSCC both in vitro and in vivo. Most notably, NLRP3 downregulation reduced the resistance of OSCC to 5-FU., Conclusions: Together, our findings demonstrate a novel approach to enhance the therapeutic efficacy and reduce the drug resistance of cancer cells to chemotherapeutic agents, which provides proof-of-concept evidence for the future development of PDEVs-enhanced therapy., (© 2021. The Author(s).)

Momordica charantia, a medicinal and edible species of the Cucurbitaceae family, has been widely used as a vegetable around the world. Hundreds of pharmacological compounds isolated from the M. charantia have been reported. However, the mechanism of action of the secondary metabolites has not been fully elucidated. In this study, 118,590 unigenes were gained by de novo assembly based on the raw data from high-throughput sequencing of mRNA (RNA-Sequencing) upon systemic analysis, among which, 51,860 (43.73%) could be annotated to the public sequence databases such as Nr, GO, Swiss-Prot, KEGG and KOG. The transcriptomic changes of M. charantia seedlings treated with or without methyl jasmonate (MeJA) were analyzed to identify key genes involved in MeJA treatment. Additionally, 554 differentially expressed genes (DEGs), including 328 up-regulated ones and 226 down-regulated genes, have been identified. Most DEGs were associated with secondary metabolism and stress responses. Meanwhile, six DEGs were further confirmed by quantitative real-time RT-PCR (qRT-PCR) analysis, resulting in similar expression patterns as compared to those of RNA-Sequencing. Nine significantly enriched pathways including 11 DEGs were identified to be possibly involved in the MeJA-responsive biosynthesis of secondary metabolites based on the transcriptome sequencing analysis. Among them, 4 DEGs, encoding two peroxidases, one cinnamyl alcohol dehydrogenase and one hypothetical protein Csa, might play important roles in the process of phenylpropanoid biosynthesis. In addition, 9 transcription factors (TFs) were also detected as DEGs from 1899 unigenes. Most of them up-regulated by MeJA treatment might be potentially involved in regulating secondary metabolites biosynthesis. This work is the first research on the large-scale assessment of M. charantia transcriptomic resources and the analysis of DEGs and TFs in secondary metabolites biosynthesis of M. charantia seedings treated with or without MeJA, which will be conducive to the further applications of M. charantia., (Copyright © 2020. Published by Elsevier B.V.)

Ascorbic acid is an organic compound with antioxidant properties that can protect the human body from the threat of free radicals. Therefore, it is important to detect the existence and measure the concentration of ascorbic acid to regulate its content in the human body. In this work, we prepared bitter gourd polysaccharide (BGP)-stabilized platinum nanoclusters (Pt-BGP NCs) by reacting BGP with K 2 PtCl 4 . Pt-BGP NCs and catalyzed the decomposition of H 2 O 2 to generate •OH radicals, which could oxidize TMB to form oxidized TMB (oxTMB), indicating their peroxidase-like properties. The kinetics followed the Michaelis-Menten equation. Furthermore, the colorimetric detection of ascorbic acid using Pt-BGP NCs showed high selectivity and a low detection limit of 0.191 μM. The accuracy of real sample detection using Pt-BGP NCs was as high as 98.9%. More importantly, Pt-BGP NCs had high cell biocompatibility and extremely low hemolysis rate due to the component of BGP. In summary, the prepared Pt-BGP NCs with reductive activity and good biocompatibility have good application prospects in colorimetric detection of ascorbic acid.

Exploiting plant extracts to form metallic nanoparticles has been becoming the promising alternative routes of chemical and physical methods owing to environmentally friendly and abundantly renewable resources. In this study, Momordica charantia and Psidium guajava leaf extract (MC.broth and PG.broth) are exploited to fabricate two kinds of biogenic silver nanoparticles (MC.AgNPs and PG.AgNPs). Phytoconstituent screening is performed to identify the categories of natural compounds in MC.broth and PG.broth. Both extracts contain wealthy polyphenols which play a role of reducing agent to turn silver (I) ions into silver nuclei. Trace alkaloids, rich saponins and other oxygen-containing compounds creating the organic corona surrounding nanoparticles act as stabilizing agents. MC.AgNPs and PG.AgNPs are characterized by UV-vis and FTIR spectrophotometry, EDS and TEM techniques. FTIR spectra indicate the presence of O-H, C = O, C-O-C and C = C groups on the surface of silver nanoparticles which is corresponded with three elements of C, O and Ag found in EDS analysis. TEM micrographs show the spherical morphology of MC.AgNPs and PG.AgNPs. MC.AgNPs were 17.0 nm distributed in narrow range of 5-29 nm, while the average size of PG.AgNPs were 25.7 nm in the range of 5-53 nm. Further, MC.AgNPs and PG.AgNPs exhibit their effectively inhibitory ability against A. niger, A. flavus and F. oxysporum as dose-dependence. Altogether, MC.AgNPs and PG.AgNPs will have much potential in scaled up production and become the promising fungicides for agricultural applications., Competing Interests: The authors have declared that no competing interests exist.

Cutibacterium acnes (formerly Propionibacterium acnes ) is a key pathogen involved in the development and progression of acne inflammation. The numerous bioactive properties of wild bitter melon (WBM) leaf extract and their medicinal applications have been recognized for many years. In this study, we examined the suppressive effect of a methanolic extract (ME) of WBM leaf and fractionated components thereof on live C. acnes -induced in vitro and in vivo inflammation. Following methanol extraction of WBM leaves, we confirmed anti-inflammatory properties of ME in C. acnes -treated human THP-1 monocyte and mouse ear edema models. Using a bioassay-monitored isolation approach and a combination of liquid-liquid extraction and column chromatography, the ME was then separated into n -hexane, ethyl acetate, n -butanol and water-soluble fractions. The hexane fraction exerted the most potent anti-inflammatory effect, suppressing C. acnes -induced interleukin-8 (IL-8) production by 36%. The ethanol-soluble fraction (ESF), which was separated from the n -hexane fraction, significantly inhibited C. acne s-induced activation of mitogen-activated protein kinase (MAPK)-mediated cellular IL-8 production. Similarly, the ESF protected against C. acne s-stimulated mouse ear swelling, as measured by ear thickness (20%) and biopsy weight (23%). Twenty-four compounds in the ESF were identified using gas chromatograph-mass spectrum (GC/MS) analysis. Using co-cultures of C. acnes and THP-1 cells, β-ionone, a compound of the ESF, reduced the production of IL-1β and IL-8 up to 40% and 18%, respectively. β-ionone also reduced epidermal microabscess, neutrophilic infiltration and IL-1β expression in mouse ear. We also found evidence of the presence of anti-inflammatory substances in an unfractionated phenolic extract of WBM leaf, and demonstrated that the ESF is a potential anti-inflammatory agent for modulating in vitro and in vivo C. acnes -induced inflammatory responses.

To gain a better insight into the selenium nanoparticle (nSe) benefits/toxicity, this experiment was carried out to address the behavior of bitter melon seedlings to nSe (0, 1, 4, 10, 30, and 50 mgL-1) or bulk form (selenate). Low doses of nSe increased biomass accumulation, while concentrations of 10 mgL-1 and above were associated with stem bending, impaired root meristem, and severe toxicity. Responses to nSe were distinct from that of bulk in that the nano-type exhibited a higher efficiency to stimulate growth and organogenesis than the bulk. The bulk form displayed higher phytotoxicity than the nano-type counterpart. According to the MSAP-based analysis, nSe mediated substantial variation in DNA cytosine methylation, reflecting the epigenetic modification. By increasing the concentration of nSe, the expression of the WRKY1 transcription factor linearly up-regulated (mean = 7.9-fold). Transcriptions of phenylalanine ammonia-lyase (PAL) and 4-Coumarate: CoA-ligase (4CL) genes were also induced. The nSe treatments at low concentrations enhanced the activity of leaf nitrate reductase (mean = 52%) in contrast with the treatment at toxic concentrations. The toxic concentration of nSe increased leaf proline concentration by 80%. The nSe supplement also stimulated the activities of peroxidase (mean = 35%) and catalase (mean = 10%) enzymes. The nSe-treated seedlings exhibited higher PAL activity (mean = 39%) and soluble phenols (mean = 50%). The nSe toxicity was associated with a disrupted differentiation of xylem conducting tissue. The callus formation and performance of the explants originated from the nSe-treated seedlings had a different trend than that of the control. This experiment provides new insights into the nSe-associated advantage/ cytotoxicity and further highlights the necessity of designing convincing studies to introduce novel methods for plant cell/tissue cultures and agriculture., Competing Interests: The authors have declared that no competing interests exist.

Low temperature is one of the abiotic factors limiting germination, growth and distribution of the plant in current plant-products industry, especially for the tropical vegetables in non-tropical area or other fields under cold temperature. Screening the plant with ability against cold temperature captured worldwide attention and exerted great importance. In our previous work, the anti-cold specie of Momordica Charantia L. seedlings was screened out. Yet, the molecular and physiological mechanisms underlying this adaptive process still remain unknown. This study was aimed to investigate adaption mechanism of anti-cold species of Momordica Charantia L. seedlings in genetical and metabolomics levels. Two species, cold-susceptible group (Y17) and cold-resistant group (Y54), were evaluated containing the indexes of malondialdehyde (MDA), hydrogen peroxide (H2O2), proline content, activities of antioxidant enzymes, metabolites changes and genes differentiation in plant tissues after cold treatment. It found that low temperature stress resulted in increased accumulation of MDA, H2O2 and proline content in two species, but less expressions in cold-resistant species Y54. As compared to Y17, cold-resistant species Y54 presented significantly enhanced antioxidant enzyme activities of POD (peroxidase), CAT (cataalase) and SOD (superoxide dismutase). Meanwhile, higher expressed genes encoded antioxidant enzymes and transcription factors when exposure to the low temperature were found in cold-resistant species Y54, and core genes were explored by Q-PCR validation, including McSOD1, McPDC1 and McCHS1. Moreover, plant metabolites containing amino acid, sugar, fatty acid and organic acid in Y54 were higher than Y17, indicating their important roles in cold acclimation. Meanwhile, initial metabolites, including amimo acids, polypeptides, sugars, organic acids and nucleobases, were apparently increased in cold resistant species Y54 than cold susceptible species Y17. Our results demonstrated that the Momordica Charantia L. seedlings achieved cold tolerance might be went through mobilization of antioxidant systems, adjustment of the transcription factors and accumulation of osmoregulation substance. This work presented meaning information for revealing the anti-cold mechanism of the Momordica Charantia L. seedlings and newsight for further screening of anti-cold species in other plant., Competing Interests: The authors have declared that no competing interests exist.

This study was designed to establish a real-time quantitative polymerase chain reaction (qPCR) method to rapidly and reliably analyze the hypoglycemic polypeptide-P gene expression pattern in Momordica charantia (MC) and to examine its expression changes in different MC accessions, harvesting seasons, and tissue types. The qPCR results were further verified by using Western blotting (WB). A total of 10 MCs with different accessions were collected and tested in this study. Among the tested accessions, RU5H showed the highest expression level of the polypeptide-P gene. The expression level of the polypeptide-P gene was not only season-related (with the highest in early July) but also tissue-related (with the highest in the seed tissue). In addition, the expression characteristic of the polypeptide-P gene was maturity-related, with the highest expression level in the tender MC. The WB results show that the transcription level of this gene shows an almost similar trend to the corresponding protein expression level. In conclusion, the established qPCR method can rapidly and effectively detect the expression levels of the polypeptide-P gene in MCs with different accessions; furthermore, various factors, including the accessions, harvesting seasons, and tissue types can affect the expression level.

The current study was designed to characterize the metabolite profile and bioactivity of two commercial bitter melon (Momordica charantia Linn.) genotypes. UPLC-high resolution mass spectrometry (HRMS) was used to identify 15 phenolic and 46 triterpenoids in various bitter melon extracts. Total phenolic levels were the highest (57.28 ± 1.02) in methanolic extract of the inner tissue of Indian Green cultivar, which also correlated to the highest DPPH radical scavenging activity (30.48 ± 2.49 ascorbic acid equivalents (mg of AAE)/g of FD). In addition, highest levels of total saponins were observed in chloroform extract of the Chinese bitter melon pericarp (75.73 mg ± 4.67 diosgenin equivalents (DE)/g of FD). Differential inhibition of α-amylase and α-glucosidase activity was observed in response to polarity of extract, cultivar and tissue type. These results suggest that consumption of whole bitter melon may have potential health benefits to manage diabetes., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Introduction: Bitter melon (Momordica charantia, Cucurbitaceae) is a popular edible medicinal plant, which has been used as a botanical dietary supplement for the treatment of diabetes and obesity in Chinese folk medicine. Previously, our team has proved that cucurbitanes triterpenoid were involved in bitter melon's anti-diabetic effects as well as on increasing energy expenditure. The triterpenoids composition can however be influenced by changes of varieties or habitats., Objectives: To clarify the significance of bioactive metabolites diversity among different bitter melons and to provide a guideline for selection of bitter melon varieties, an exploratory study was carried out using a UHPLC-HRMS based metabolomic study to identify chemotypes., Methods: Metabolites of 55 seed samples of bitter melon collected in different parts of China were profiled by UHPLC-HRMS. The profiling data were analysed with multivariate (MVA) statistical methods. Principle component analysis (PCA) and hierarchical cluster analysis (HCA) were applied for sample differentiation. Marker compounds were identified by comparing spectroscopic data with isolated compounds, and additional triterpenes were putatively identified by propagating annotations through a molecular network (MN) generated from UHPLC-HRMS & MS/MS metabolite profiling., Results: PCA and HCA provided a good discrimination between bitter melon samples from various origins in China. This study revealed for the first time the existence of two chemotypes of bitter melon. Marker compounds of those two chemotypes were identified at different MSI levels. The combined results of MN and MVA demonstrated that the two chemotypes mainly differ in their richness in cucurbitane versus oleanane triterpenoid glycosides (CTGs vs. OTGs)., Conclusion: Our finding revealed a clear chemotype distribution of bioactive components across bitter melon varieties. While bioactivities of individual CTGs and OTGs still need to be investigated in more depth, our results could help in future the selection of bitter melon varieties with optimised metabolites profile for an improved management of diabetes with this popular edible Chinese folk medicine.

Debittered bitter gourd juice was subjected to gamma irradiation doses of 0, 0.25, 0.5, 0.75, 1, 1.5 and 2.5 kGy and thermal pasteurization at temperatures of 65, 75, 85 and 95 °C. Shigella boydii was the most heat resistant pathogen tested (D 10 of 42.8 s at 65 °C) while Bacillus cereus was the most resistant pathogen to irradiation with a D 10 of 0.46 kGy. No significant (p < 0.05) effect of thermal pasteurization was observed on antidiabetic (α-amylase and α-glucosidase inhibition) activity, however, a 10% increase in α-glucosidase inhibition was observed in irradiated (2.5 kGy) samples. A significant (p < 0.05) but marginal reduction (up to 10%) was observed in antidiabetic activity during storage for a period of 90 days. Thermal pasteurization at 65 °C demonstrated significantly (p < 0.05) higher sensory quality as compared to irradiated (2.5 kGy) samples. This is first report on effect of pasteurization on antidiabetic activity of bitter gourd juice., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Heat stress adversely affects plant physiological and metabolic processes and is considered an important constraint on crop growth and productivity in agriculture worldwide. Grafting techniques are capable of mitigating various stresses. Here, compared with self-grafted cucumbers subjected to 42 °C heat stress for 24 h, we found that Momordica-grafted cucumbers exhibited higher cytomembrane thermostability, less photoinhibition reflected by their chlorophyll fluorescence, and a reduction in oxidative stress. To better understand the mechanism, optimized Blue-Native/SDS-PAGE two-dimensional electrophoresis (2-DE) was firstly applied to entire thylakoid membrane of grafted cucumbers, and 25 significantly differential accumulated protein spots were identified by MALDI-TOF/TOF MS analysis. The proteomic analysis revealed that high temperatures suppressed the accumulation of 13 proteins in self-grafted cucumbers, while Momordica rootstock stimulated the accumulation of 12 of these proteins. The transcriptional analysis indicated that grafting onto Momordica significantly increased the expression of genes that encode the photosystem II subunit S (PsbS) and minor light-harvesting complexes (CP24, CP26 and CP29.1), which are closely associated with non-photochemical quenching (NPQ) after heat shock. Immunoblotting for PsbS corroborated the Momordica-induced acceleration of heat dissipation. Taken together, Momordica rootstock alleviated heat-induced photoinhibition by maintaining intracellular redox homeostasis, stabilizing the protein library of the thylakoid membrane and modulating NPQ in the scions., (Copyright © 2019 Elsevier Masson SAS. All rights reserved.)

Loss of skeletal muscle mass and strength is often associated with disability and poor quality of life. Selective Androgen Receptor Modulators (SARMs) are under development as potential treatment. This study aims at examining the potential of wild bitter gourd (BG) as a SARM and its effects on the muscle decline induced by orchiectomy. In the cell-based androgen receptor (AR) transactivation assay, the BGP extract showed weak agonistic and antagonistic activities, resembling those of some SARMs. Male C57BL/6J mice were sham-operated (Sham group) or castrated (Cast groups) and fed a modified AIN-93G high sucrose diet supplemented without (Cast group) or with 5% lyophilized BG powder (Cast + BGP) or with testosterone propionate (7 mg TP per kg diet, Cast + TP) for 23 weeks. In contrast to the Cast + TP group, the BGP supplementation did not affect the serum testosterone concentration, and prostate and seminal vesicle mass. Both TP and BGP supplementation increased the weight of androgen responsive muscles, bulbocavernosus (BC) and levator ani (LA) (p < 0.05). The grip strength and the performance on a rotarod of the Cast + BGP group were comparable to those of the Cast + TP group (p > 0.05). The number of succinate dehydrogenase (SDH)-positive fibers of the Cast + BGP group was not significantly different from that of the Sham and Cast + TP groups (p > 0.05). The BGP supplementation up-regulated the Pgc1α, Ucp2 or Ucp3 gene expressions in skeletal muscles of castrated mice (p < 0.05). BGP showed some characteristics of the SARM and might improve skeletal muscle function through the up-regulation of mitochondrial biogenic genes and oxidative capacity, and ameliorated the castration-induced decline of skeletal muscle function in mice.

Momordica charantia (M. charantia) has been widely used to treat obesity due to its bioactive ingredients. This research aimed to investigate the anti-obesity effect of polysaccharides (FP) from fermented M. charantia with Lactobacillus plantarum NCU116 on high-fat induced obese rats. We found that FP could effectively lower the body weight gain, Lee's index, insulin resistance and cell sizes of epididymal adipose tissues in obese rats compared with polysaccharides from non-fermented M. charantia (NFP). FP treatments decreased the total cholesterol, triacylglycerols, and low-density lipoprotein cholesterol, leptin, whereas they elevated the high-density lipoprotein cholesterol, adiponectin, significantly in the serum of obese rats. Furthermore, administrations of FP notably improved oxidative balance in obese rats. Lipidomics results indicated that 24 potential biomarkers have been identified in serum. Additionally, 21 lipids were considerably altered by FP and NFP intakes, such as fatty acyls, glycerolipids, sphingolipids, sterol lipids and glycerophospholipids. The anti-obesity properties of FP were revealed via relieving insulin resistance and fat accumulation of obese rats, which was associated with the regulation of lipid metabolism. Overall, FP exerted more favourable impacts on the anti-obesity effect than NFP, which may be attributed to fermentation.

Obesity is known to induce pathological changes in the gut and diets rich in complex carbohydrates that resist digestion in the small bowel can alter large bowel ecology. The purposes of this study were to identify the effects of bitter melon powder (BMP) on the global gene expression pattern in the colon mucosa of obese rats. Obese rats were fed a high-fat diet and treated without or with BMP for 8 weeks. Genome-wide expression profiles of the colon mucosa were determined by RNA sequencing (RNA-Seq) analysis at the end of experiment. A total of 87 genes were identified as differentially expressed (DE) between these two groups (fold change > 1.2). These results were further validated by quantitative RT-PCR, confirming the high reliability of the RNA-Seq. Interestingly, DE genes implicated in inflammation and lipid metabolism were found to be downregulated by BMP in the colon. Network between genes and the top 15 KEGG pathways showed that PRKCβ (protein kinase C beta) and Pla2g2a (phospholipase A2 group IIA) strongly interacted with surrounding pathways and genes. Results revealed that BMP supplement could remodel key colon functions by altering transcriptomic profile in obese rats.

Background: The elemental uptake and allocation patterns of crops create insight for nutrient management. Two-year field experiments were conducted to determine the growth and nitrogen (N) uptake patterns of bitter gourd and to evaluate different N management strategies. Two N practices during the nursery stage, namely the conventional fertilizer method (Scon) and the controlled-release fertilizer management method (Scrf), combined with three N management strategies after transplanting, namely zero N fertilizer application (Nno), the conventional strategy (Ncon) and the systematic N management strategy (Nopt), were assessed., Results: Averaged over two years, the Scrf-Nopt treatment performed best, producing 33.1 t ha -1 fruit yield with 310 kg N ha -1 , indicating that the yield was 22.6% greater by using 18.8% less fertilizer N than in the Scon-Ncon treatment. The Scrf-Nopt treatment facilitated plant growth by accumulating 20.0% more total dry weight and prioritized its allocation to productive organs (57.2%), while the Scon-Ncon strategy was biased toward leaves (56.3%) over fruits (43.8%). Nitrogen uptake and distribution closely followed the pattern of biomass., Conclusion: The Scrf-Nopt fertilization strategy coordinated the important role that N plays in total accumulation and well proportion of biomass and N in bitter gourd developmental processes. © 2017 Society of Chemical Industry., (© 2017 Society of Chemical Industry.)

Previous study reported a novel type of self-discrimination in the tendrils of the vine Cayratia japonica (Vitaceae). However, whether self-discrimination in tendrils is common in vine plant species has not been elucidated. Here, we investigated whether tendrils of Momordica charantia var. pavel (Cucurbitaceae), Cucumis sativus (Cucurbitaceae) and Passiflora caerulea (Passifloraceae) can discriminate self and non-self plants. We also investigated whether the tendrils of M. charantia and C. sativus can discriminate differences in cultivars to determine the discrimination ability for genetic similarity. We found that tendrils of the M. charantia and P. caerulea were more likely to coil around non-self plant than self plants, but not in C. sativus. Our findings support the common occurrence of self-discrimination in tendrils in different plant taxa, although some species lacked it. Furthermore, tendrils of M. charantia more rapidly coil around different cultivars than around same cultivars. The tendrils of M. charantia may can discriminate differences in cultivars.

Charantin, a natural cucurbitane type triterpenoid, has been reported to have beneficial pharmacological functions such as anticancer, antidiabetic, and antibacterial activities. However, accumulation of charantin in bitter melon has been little studied. Here, we performed a transcriptome analysis to identify genes involved in the triterpenoid biosynthesis pathway in bitter melon seedlings. A total of 88,703 transcripts with an average length of 898 bp were identified in bitter melon seedlings. On the basis of a functional annotation, we identified 15 candidate genes encoding enzymes related to triterpenoid biosynthesis and analyzed their expression in different organs of mature plants. Most genes were highly expressed in flowers and/or fruit from the ripening stages. An HPLC analysis confirmed that the accumulation of charantin was highest in fruits from the ripening stage, followed by male flowers. The accumulation patterns of charantin coincide with the expression pattern of McSE and McCAS1, indicating that these genes play important roles in charantin biosynthesis in bitter melon. We also investigated optimum light conditions for enhancing charantin biosynthesis in bitter melon and found that red light was the most effective wavelength.

Background: Our present study was conducted to characterize the phytoconstituents present in the aqueous extract of Momordica charantia and evaluate the antimicrobial efficacy of silver-extract nanoparticles (Ag-Extract-NPs)., Methods: Silver nanoparticles (AgNPs) were prepared by reducing AgNO 3; and NaBH 4 served as reducing agent. After screening of phytochemicals; AgNPs and aqueous extract were mixed thoroughly and then coated by polyaniline. These NPs were characterized by using Visual inspection, UV spectroscopy, FTIR, SEM and TEM techniques. Antimicrobial activities were assessed against Staphylococcus aureus, Salmonella typhi, Escherichia coli and Pseudomonas aeruginosa., Results: Aqueous extract of M. charantia fruits contain alkaloid, phenol, saponin etc. UV-Vis spectrum showed strong absorption peak around 408 nm. The presence of -CH, -NH, -COOH etc. stretching in FTIR spectrum of Ag-Extract-NPs endorsed that AgNPs were successfully capped by bio-compounds. SEM and TEM result revealed that synthesized NPs had particle size 78.5-220 nm. Ag-Extract-NPs showed 34.6 ± 0.8 mm zone of inhibition against E. coli compared to 25.6 ± 0.5 mm for ciprofloxacin. Maximum zone of inhibition for Ag-Extract-NPs were 24.8 ± 0.7 mm, 26.4 ± 0.4 mm, 7.4 ± 0.4 mm for S. aureus, P. aeruginosa and S. typhi. We found that Ag-Extract-NPs have much better antibacterial efficacy than AgNPs and M. charantia extract has individually. It is also noticed that gram negative bacteria (except S. typhi) are more susceptible to Ag-Extract-NPs than gram positive bacteria., Conclusion: Ag-Extract-NPs showed strong antibacterial activity. In order to make a reliable stand for mankind, further study is needed to consider determining the actual biochemical pathway by which AgNPs-extracts exert their antimicrobial effect.

Background: Hypercholesterolemia is a serious diseases associated with type-2 diabetes, atherosclerosis, cardiovascular disorders and liver diseases. Humans seek for safe herbal medication such as karela (Momordica charantia/bitter melon) to treat such disorders to avoid side effect of pharmacotherapies widely used., Methods: Forty male Wistar rats were divided into four equal groups; control group with free access to food and water, cholesterol administered group (40 mg/kg BW orally); karela administered group (5 g /kg BW orally) and mixture of cholesterol and karela. The treatments continued for 10 weeks. Karela was given for hypercholesterolemic rats after 6 weeks of cholesterol administration. Serum, liver and epididymal adipose tissues were taken for biochemical, histopathological and genetic assessments., Results: Hypercholesterolemia induced a decrease in serum superoxide dismutase (SOD), catalase, reduced glutathione (GSH) and an increase in malondialdehyde (MDA) levels that were ameliorated by karela administration. Hypercholesterolemia up regulated antioxidants mRNA expression and altered the expression of carbohydrate metabolism genes. In parallel, hypercholesterolemic groups showed significant changes in the expression of PPAR-alpha and gamma, lipolysis, lipogenesis and cholesterol metabolism such as carnitine palmitoyltransferase-1 (CPT-1). Acyl CoA oxidase (ACO), fatty acids synthase (FAS), sterol responsible element binding protein-1c (SREBP1c), 3-hydroxy-3-methylglutaryl coenzyme A reductase (HMG-CoAR) and cholesterol 7α-hydroxylase (CYP7A1) at hepatic and adipose tissue levels. Interestingly, Karela ameliorated all altered genes confirming its hypocholesterolemic effect. Histopathological and immunohistochemical findings revealed that hypercholesterolemia induced hepatic tissue changes compared with control. These changes include cholesterol clefts, necrosis, karyolysis and sever congestion of portal blood vessel. Caspase-3 immunoreactivity showed positive expression in hepatic cells of hypercholesterolemic rats compared to control. All were counteracted and normalized after Karela administration to hypercholesterolemic group., Conclusion: Current findings confirmed that karela is a potential supplement useful in treatment of hypercholesterolemia and its associated disorders and is good for human health.

Products derived from edible medicinal plants have been used for centuries to prevent, treat, and even cure multiple diseases. Momordica charantia L., widely cultivated around the world, is a typical one bred for vegetables and medicinal usage. All parts of M. charantia possess important medicinal properties, including antidiabetic, anticancer, hypotensive, anti-obesity, antimicrobial, antihyperlipidemic, antioxidant, anti-inflammatory, immuno-modulatory, anthelmintic, neuro-protective, as well as hepato-protective properties both in vitro and in vivo. This review summarizes the active components and medicinal properties of M. charantia, especially the activities and mechanisms of its anti-diabetic and anti-cancer properties. The anti-diabetic properties involve inhibiting intestinal α-glucosidase and glucose transport, protecting islet β-cells, enhancing insulin secretion, increasing hepatic glucose disposal, decreasing gluconeogenesis, and even ameliorating insulin resistance. Moreover, the expressions of PPARs could also be activated and up-regulated. Meanwhile, its anticancer properties are mostly due to apoptosis, cell cycle arrest, and expression of serum factors associated with immunity. In this review, we aim to provide an overview of M. charantia and its benefits for development as a functional food.

In general, salinity and heavy metals interfere with several physiological processes and reduce plant growth. In order to evaluate of three levels of salinity (0, 4 and 8 ds m(-1)) and three concentration of chromium (0, 10 and 20 mg kg(-1) soil) in bitter melon (Momordica charantia), a plot experiment was conducted in greenhouse at university of Shahrood, Iran. The results revealed that chromium treatment had no significant affect on fresh and dry weight, but salinity caused reduction of fresh and dry weight in growth parameter. Salinity and chromium enhanced antioxidant enzymes activities like catalase (CAT), guaiacol peroxidase (GPX) and sodium content in leaves. However salinity and chromium treatments had no effect on potassium, phosphorus in leaves, soluble carbohydrate concentration in leaves and root, but decreased the carotenoid content in leaves. On increasing salinity from control to 8 ds m(-1) chlorophyll a, b and anthocyanin content decreased by 41.6%, 61.1% and 26.5% respectively but chromium treatments had no significant effect on these photosynthetic pigments.

Background: Momordica charantia (MC) is an edible medicinal plant that is known for its diversified biological functions. Momordica Antiviral Protein 30kD (MAP30) is a type I single chain ribosome-inactivating protein (RIP) isolated from the mature fruit and seeds of MC. Since MAP30 content in MC is limited, the study aim was to generate the recombinant MAP30 protein using prokaryotic expression system and determine its apoptotic/growth inhibitory effects on bladder cancer 5637 cells., Methods: MAP30 gene was amplified by PCR from MC genomic DNA and identified by sequencing. The target gene was inserted into pET-28a (+) vector and transformed into E. coli BL21 (DE3) cells. Positive clones were selected by PCR. Recombinant protein was efficiently expressed under induction with 1.0 mM Isopropylthio-β-D-galactoside (IPTG) at 30° C for 4 hours. Cytotoxicity studies were performed using MTT assay by treating 5637 bladder cancer cells with 100 µg/mL, 200 µg/mL, and 400 µg/mL concentrations of MAP30 for 24 hours and 48 hours, respectively. Flow cytometry was used to measure the apoptosis of MAP30-treatedcells in time course experiments., Results: Full-length MAP30 gene was successfully expressed in Escherichia coli (E. coli) BL21 strain and MAP30 recombinant protein inhibited the growth of bladder cancer 5637 cells at 200 µg/mL and 400 µg/mL concentrations by inducing apoptosis of target cells in a dose- and time-dependent manner., Conclusion: It was, therefore, concluded that the MAP30 recombinant protein displayed potent antitumor activity in vitro.

Momordica anti-human immunodeficiency virus protein of 30 kDa (MAP30) has been shown to exhibit potent antitumor activities against several solid tumors. In the present investigation we demonstrated that MAP30 significantly inhibited the proliferation of acute myeloid leukemia (AML) HL-60 and THP-1 cell lines and patient AML cells through autophagy inhibition and apoptosis induction. Intriguingly, MAP30-induced cell death and apoptosis were partially rescued in combination with an autophagy activator rapamycin, and aggravated in combination with an autophagy inhibitor bafilomycin A1 in HL-60 cells, suggesting that autophagy is a pro-survival signal and its inhibition contributes to the induction of apoptosis in MAP30‑induced cell death. Further mechanism analysis demonstrated that MAP30 enhanced p300, and C646, a selective inhibitor of p300, markedly promoted autophagy and partially rescued the MAP30-induced cell death in HL-60 cells and patient AML cells. Collectively, our findings suggest that apoptosis and autophagy act cooperatively to elicit MAP30-induced cell death and MAP30 may be a potential antitumor drug candidate against AML.

Protein-ligand docking is a commonly used method for lead identification and refinement. While traditional structure-based docking methods represent the receptor as a rigid body, recent developments have been moving toward the inclusion of protein flexibility. Proteins exist in an interconverting ensemble of conformational states, but effectively and efficiently searching the conformational space available to both the receptor and ligand remains a well-appreciated computational challenge. To this end, we have developed the Flexible CDOCKER method as an extension of the family of complete docking solutions available within CHARMM. This method integrates atomically detailed side chain flexibility with grid-based docking methods, maintaining efficiency while allowing the protein and ligand configurations to explore their conformational space simultaneously. This is in contrast to existing approaches that use induced-fit like sampling, such as Glide or Autodock, where the protein or the ligand space is sampled independently in an iterative fashion. Presented here are developments to the CHARMM docking methodology to incorporate receptor flexibility and improvements to the sampling protocol as demonstrated with re-docking trials on a subset of the CCDC/Astex set. These developments within CDOCKER achieve docking accuracy competitive with or exceeding the performance of other widely utilized docking programs., (© 2015 Wiley Periodicals, Inc.)

The antitumor activity of 3β,7β,25-trihydroxycucurbita-5,23(E)-dien-19-al (TCD), a triterpenoid isolated from wild bitter gourd, in breast cancer cells was investigated. TCD suppressed the proliferation of MCF-7 and MDA-MB-231 breast cancer cells with IC50 values at 72 h of 19 and 23 μM, respectively, via a PPARγ-independent manner. TCD induced cell apoptosis accompanied with pleiotrophic biological modulations including down-regulation of Akt-NF-κB signaling, up-regulation of p38 mitogen-activated protein kinase and p53, increased reactive oxygen species generation, inhibition of histone deacetylases protein expression, and cytoprotective autophagy. Together, these findings provided the translational value of TCD and wild bitter gourd as an antitumor agent for patients with breast cancer.

Silver nanoparticles (AgNPs) were prepared through green route with the aid of Momordica charantia leaf extract as both reductant and stabilizer. X-ray diffraction pattern (XRD) and selected area electron diffraction (SAED) fringes revealed the structure of AgNPs as face centered cubic (fcc). Morphological studies elucidate the nearly spherical AgNPs formation with particle size in nanoscale. Biosynthesized AgNPs were found to be photoluminescent and UV-Vis absorption spectra showed one surface plasmon resonance peak (SPR) at 424nm attesting the spherical nanoparticles formation. XPS study provides the surface chemical nature and oxidation state of the synthesized nanoparticles. FTIR spectra ascertain the reduction and capping nature of phytoconstituents of leaf extract in AgNPs synthesis. Further, these AgNPs showed effective antimicrobial activity against tested pathogens and thus applicable as potent antimicrobial agent. In addition, the synthesized AgNPs were observed to have an excellent catalytic activity on the reduction of methylene blue by M. charantia which was confirmed by the decrement in maximum absorbance values of methylene blue with respect to time and is ascribed to electron relay effect., (Copyright © 2015 Elsevier B.V. All rights reserved.)

Background: Bitter melon (Momordica charantia L.) is a medicinal fruit reported to have antidiabetic properties. To grow this tropical fruit year-round in temperate climates, greenhouse production is necessary, sometimes without insect pollinators. Suitable high-yielding varieties with good bioactivity need to be identified. This experiment evaluated the yield of six varieties of bitter melon under greenhouse conditions and their bioactivity in terms of total phenolic and saponin compounds and total antioxidant activity determined using four assays., Results: The larger varieties (Big Top Medium, Hanuman, Jade and White) were more productive than the small varieties (Indra and Niddhi) in terms of total fruit weight and yield per flower pollinated. The bioactivity (total phenolic and saponin compounds and antioxidant activity) of the two small varieties and Big Top Medium was significantly higher than that of the other three large varieties. Two antioxidant assays, 2,2-diphenyl-1-picrylhydrazyl (DPPH) and ferric-reducing antioxidant power (FRAP), were shown to provide the strongest correlations with phenolic and saponin compounds of bitter melon., Conclusion: Preliminary research has identified Big Top Medium as the most suitable variety for greenhouse production. The rich source of phenolic and saponin compounds and their associated antioxidant activity highlight bitter melon as a valuable food., (© 2013 Society of Chemical Industry.)

This study aimed to investigate the changes in the proteome of bitter gourd prior to and after subjecting to boiling and microwaving. A comparative analysis of the proteome profiles of raw and thermally treated bitter gourds was performed using 2D-DIGE. The protein content and number of protein spots in raw sample was higher when compared to the cooked samples. Qualitative analysis revealed that 103 (boiled sample) and 110 (microwaved sample) protein spots were up regulated whereas 120 (boiled sample) and 107 (microwaved sample) protein spots were down regulated. Ten protein spots with the highest significant fold change in the cooked samples were involved in carbohydrate/energy metabolisms and stress responses. Small heat shock proteins, superoxide dismutase, quinone oxidoreductase, UDP-glucose pyrophosphorylase and phosphoglycerate kinase play a role in heat-stress-mediated protection of bitter gourd. This study suggests that appropriate heat treatment (cooking methods) can lead to induction of selected proteins in bitter gourd., (Copyright © 2013 Elsevier Ltd. All rights reserved.)

A multitude of plants have been used extensively for the treatment of cancers throughout the world. The protein, α, β momorcharin has been extracted from the plant Momordica charantia (MC), and it possesses anti-cancer and anti-HIV properties similar to the crude water and methanol soluble extract of the plant. This study investigated the anti-cancer effects and the cellular mechanisms of action of α, β momocharin (200-800 μM) on 1321N1, Gos-3, U87-MG, Sk Mel, Corl-23 and Weri Rb-1 cancer cell lines compared to normal healthy L6 muscle cell line measuring cell viability using MTT assay kit, Caspase-3 and 9 activities, cytochrome c release and intracellular free calcium concentrations [Ca(2+)]i. The results show that α, β momorcharin can evoke significant dose-dependent (P < 0.05; Student's t test) decreases in the viability (increases in cell death) of 1321N1, Gos-3, U87-MG, Sk Mel, Corl-23 and Weri Rb-1 cancer cell lines compared to healthy L6 muscle cell line and untreated glioma cells. α, β momorcharin (800 μM) also evoked significant (P < 0.05) increases in caspase-3 and 9 activities and cytochrome c release. Similarly, α, β momorcharin elicited significant (P < 0.05) time-dependent elevation in [Ca(2+)]i in all five glioma cell lines compared to untreated cells. Together, the results have demonstrated that α, β momorcharin can exert its anti-cancer effect on different cancer cell lines by intracellular processes involving an insult to the mitochondria resulting in cellular calcium over loading, apoptosis, cytochrome release and subsequently, cell death.

We sought to evaluate the effects of Momordica charantia (bitter melon, BM) extract on insulin sensitivity, NAFLD, hepatic FGF21 and AMPK signaling in mice fed a high-fat diet. Male C57/B6 mice were randomly divided into HFD and HFD supplementation with BM for 12 week. Body weight, plasma glucose, FGF21 and insulin levels, hepatic FGF21 and AMPK signaling proteins were measured. The results showed that plasma FGF21 and insulin concentrations were significantly decreased and hepatic FGF21 content was significantly down-regulated, while FGF receptors 1, 3 and 4 (FGFR1, FGFR3 and FGFR4) were greatly up-regulated in BM group compared to the HFD group (P < 0.05 and P < 0.01). BM also significantly increased hepatic AMPK p, AMPK α1 AMPK α2 and Sirt1 content compared to the HFD mice. We, for the first time, demonstrated that BM extract attenuated hepatic steatosis in mice by enhancing hepatic FGF21 and AMPK/Sirt1 signaling.

Background: Recent research on nanoparticles in a number of crops has evidenced for enhanced germination and seedling growth, physiological activities including photosynthetic activity and nitrogen metabolism, mRNA expression and protein level, and also positive changes in gene expression indicating their potential use in crop improvement. We used a medicinally rich vegetable crop, bitter melon, as a model to evaluate the effects of seed treatment with a carbon-based nanoparticle, fullerol [C60(OH)20], on yield of plant biomass and fruit characters, and phytomedicine contents in fruits., Results: We confirmed the uptake, translocation and accumulation of fullerol through bright field imaging and Fourier transform infra-red spectroscopy. We observed varied effects of seed treatment at five concentrations, including non-consequential and positive, on plant biomass yield, fruit yield and its component characters, and content of five phytomedicines in fruits. Fullerol-treatment resulted in increases up to 54% in biomass yield and 24% in water content. Increases of up to 20% in fruit length, 59% in fruit number, and 70% in fruit weight led to an improvement up to 128% in fruit yield. Contents of two anticancer phytomedicines, cucurbitacin-B and lycopene, were enhanced up to 74% and 82%, respectively, and contents of two antidiabetic phytomedicines, charantin and insulin, were augmented up to 20% and 91%, respectively. Non-significant correlation inter se plant biomass, fruit yield, phytomedicine content and water content evidenced for separate genetic control and biosynthetic pathways for production of plant biomass, fruits, and phytomedicines in fruits, and also no impact of increased water uptake., Conclusions: While our results indicated possibility of improving crop yield and quality by using proper concentrations of fullerol, extreme caution needs to be exercised given emerging knowledge about accumulation and toxicity of nanoparticles in bodily tissues.

The effect of mixed inoculums of VAM (Vesicular Arbuscular Mycorrhizas) fungi on seed growth and photosynthetic apparatus in green house was monitored. The plants were watered daily with tap water. Plants were cultivated in natural environment in mid of March (2011). A direct relation between root length and water contents suggests a defense mechanism of MP (microrihzal plants) against the fungal stress. It was also supported by the fact that the leaf area of MP was much greater as compared to the NMP (non microrihzal plants) with elevated concentration of all chlorophyllus pigments in 30 days. An increase in the surface area of the leaf and concentration of the pigments, may be for an acceleration in absorption of CO₂ for reduction of it into glucose through oxidation of water molecule. The non-significant decline in glucose contents support the above hypothesis of rapid redox reaction mechanism which was established to overcome the stress. The positive effects of mycorrhizal which were already mentioned in the literature were reported in this article in relations of survival strategies of the plant, adapted in stress conditions. An increase in the chlorophyll contents (30 d) and leaf area of plants possibly attributed with absorption of solar radiation for the protection of plants. It was also supported by the higher concentration of carotenoids (30 d) that may have an additional function of regulation of certain developmental responses and screening of light to save the plants from stress conditions.

Alpha-momorcharin (α-MC), a member of the ribosome-inactivating protein (RIP) family, has been used not only as antiviral, antimicrobial, and antitumor agents, but also as toxicant to protozoa, insects, and fungi. In this study, we expressed the protein in Escherichia coli Rosetta (DE3) pLysS strain and purified it by nickel-nitrilotriacetic acid affinity chromatography. A total of 85 mg of homogeneous protein was obtained from 1 l culture supernatant of Rosetta (DE3) pLysS, showing a high recovery rate of 73.9%. Protein activity assay indicated that α-MC had both N-glycosidase activity and DNA-nuclease activity, the former releasing RIP diagnostic RNA fragment (Endo's fragment) from rice rRNAs and the latter converting supercoiled circular DNA of plasmid pET-32a(+) into linear conformations in a concentration-dependent manner. Specially, we found that α-MC could inhibit the mycelial growth of Fusarium solani and Fusarium oxysporum with IC(50) values of 6.23 and 4.15 μM, respectively. Results of optical microscopy and transmission electron microscopy demonstrated that α-MC caused extensive septum formation, loss of integrity of the cell wall, separation of the cytoplasm from the cell wall, deformation of cells with irregular budding sites, and apoptosis in F. solani. Moreover, α-MC was active against Pseudomonas aeruginosa with an IC(50) value of 0.59 μM. The α-MC protein carries a high potential for the design of new antifungal drugs or the development of transgenic crops resistant to pathogens.

The incidence of nasopharyngeal carcinoma (NPC) remains high in endemic regions, including southern China, northern Africa, and North America. One of the promising therapeutic approaches on NPC is drug screening from natural products, such as components from traditional Chinese medicine. In this study, the antitumor activity of Momordica charantia lectin (MCL), a type II ribosome inactivating protein from bitter gourd, on NPC was investigated. MCL evinced potent cytotoxicity toward NPC CNE-1 (IC(50) = 6.9) and CNE-2 (IC(50) = 7.4) cells but minimally affected normal NP 69 cells. Further investigation disclosed that MCL induced apoptosis, DNA fragmentation, G(1)-phase arrest, and mitochondrial injury in both types of NPC cells. The reduction of cyclin D1 and phosphoretinoblastoma (Rb) protein expression contributed to arrest at G(1)-phase of the cell cycle. These events were associated with regulation of mitogen-activated protein kinases (MAPK; including p38 MAPK, JNK, and ERK) phosphorylation and promoted downstream nitric oxide (NO) production. Concurrent administration of the p38 MAPK inhibitor SB-203580 significantly diminished NO production and lethality of MCL toward NPC cells. Further studies revealed that MCL increased cytochrome c release into the cytosol, activated caspases-8, -9, and -3, and enhanced production of cleaved PARP, subsequently leading to DNA fragmentation and apoptosis. Finally, an intraperitoneal injection of MCL (1.0 mg/kg/d) led to an average of 45% remission of NPC xenograft tumors subcutaneously inoculated in nude mice. This is the first article that unveils the potential of a type II RIP, MCL, for prevention and therapy of NPC., (©2011 AACR.)